Use of particulate contrast agents in diagnostic imaging for studying physiological paramaters

Abstract

The present invention relates to a method of imaging of an animate human or non-human animal body, which method comprises: administering parenterally to said body a particulate material comprising a matrix or membrane material and at least one contrast generating species, which matrix or membrane material is responsive to a pre-selected physiological parameter whereby to alter the contrast efficacy of said species in response to a change in the value of said parameter; generating image data of at least part of said body in which said species is present; and generating therefrom a signal indicative of the value or variation of said parameter in said part of said body. The invention also relates to contrast media for imaging a physiological parameter.

1 . (canceled) 
     
     
         2 .- 23 . (canceled) 
     
     
         24 . A contrast medium for imaging of a physiological parameter, said medium comprising a particulate material comprising a matrix or membrane material and at least one magnetic resonance contrast generating species, said matrix or membrane material being responsive to a pre-selected physiological parameter and the response is an increased matrix or membrane permeability or chemical or physical breakdown of the matrix or membrane material, to cause the contrast efficacy of said contrast generating species to vary in response to said parameter. 
     
     
         25 . A contrast medium as claimed in  claim 24  wherein the matrix or membrane material is responsive to pH, temperature, pressure, carbon dioxide tension, oxygen tension, enzyme activity, tissue electrical activity, tissue water diffusion or ion concentration. 
     
     
         26 . A contrast medium as claimed in  claim 25  wherein the matrix or membrane material is responsive to pH, temperature or pressure. 
     
     
         27 . A contrast medium as claimed in  claim 24  wherein the magnetic resonance contrast generating species is selected from the group consisting of paramagnetic compounds, superparamagnetic compounds, ferrimagnetic compounds, ferromagnetic compounds and compounds containing other non-zero spin nuclei than hydrogen. 
     
     
         28 . A contrast medium as claimed in  claim 27  wherein the magnetic resonance contrast generating species is a paramagnetic compound. 
     
     
         29 . A contrast medium as claimed in  claim 28  wherein the magnetic resonance contrast generating species is a paramagnetic compound selected from the group consisting of stable free radicals, transition metal compounds and lanthanide metal compounds. 
     
     
         30 . A contrast medium as claimed in  claim 28  wherein the magnetic resonance contrast generating species is a paramagnetic compound selected from the group consisting of manganese compounds, gadolinium chelates, ytterbium chelates, dysprosium chelates and europium compounds. 
     
     
         31 . A contrast medium as claimed in  claim 27  wherein the magnetic resonance contrast generating species is a superparamagnetic metal oxide. 
     
     
         32 . A contrast medium as claimed in  claim 27  wherein the magnetic resonance contrast generating species is a compound containing other non-zero spin nuclei than hydrogen selected from the group consisting of  19 F,  13 C,  15 N,  29 Si and  31 P. 
     
     
         33 . A contrast medium as claimed in  claim 32  wherein the magnetic resonance contrast generating species is a compound containing  19 F. 
     
     
         34 . A contrast medium as claimed in  claim 32  wherein the magnetic resonance contrast generating species is a compound containing  13 C or  15 N. 
     
     
         35 . A contrast medium as claimed in  claim 32  wherein the non-zero spin nuclei are hyperpolarized nuclei. 
     
     
         36 . A contrast medium as claimed in  claim 24  wherein the matrix or membrane material is selected from lipids, phospholipids, surfactants, proteins, oligomers or physiologically acceptable polymers. 
     
     
         37 . A contrast medium as claimed in  claim 36  wherein the matrix or membrane material forms a vesicle or a liposome. 
     
     
         38 . A contrast medium as claimed in  claim 36  wherein the matrix or membrane material is responsive to pH. 
     
     
         39 . A contrast medium as claimed in  claim 36  wherein the matrix or membrane material is responsive to temperature. 
     
     
         40 . A contrast medium as claimed in  claim 39  wherein the matrix or membrane material comprises a lipid or a lipid mixture or a phospholipid or a phospholipid mixture. 
     
     
         41 . A contrast medium as claimed in  claim 40  wherein the lipid or the lipid mixture or the phospholipid or the phospholipid mixture has a Tc value between 35° C. and 80° C. 
     
     
         42 . A contrast medium as claimed in  claim 24  wherein said particulate material is in combination with a targeting ligand for a cell or receptor of interest. 
     
     
         43 . A contrast medium as claimed in  claim 24  wherein the matrix or membrane material is responsive to temperature and comprises hydrogenated phosphatidyl choline (HPC), hydrogenated phosphatidylserine-sodium (HPS), dipalmitoylphophatidylcholine (DPPC), distearyl-phosphatidylcholine (DSPC), dipalmitoylphosphatidyl-glycerol (DPPG), dipalmitoylphosphatidylethanolamine (DPPE), dibehenoylphosphatidylcholine, dimyristoyl-phosphatidyl glycerol (DMPG), cholesterol, cardiolipin and starch and the magnetic resonance contrast generating species is selected from the group consisting of superparamagnetic iron oxide, GdDTPA-BMA, GdBOPTA, GdDTPA, GdDOTA, GdHPDO3A, DyDTPA-BMA and PrDO3A.